SALT-ACTIVATED ENZYMES FOR ORGANIC SYNTHESIS

酶可以在非水介质中发挥作用的发现为极大地扩大酶在合成化学中的用途提供了可能性。然而，酶在有机介质中的活性几乎总是比在水溶液中的活性低得多。由于许多理想的酶催化转化目标不溶于水，但可溶于有机溶剂，有机介质中的低催化活性迄今限制了酶在合成化学中的商业应用。最近的研究表明，丝氨酸蛋白酶在盐基质中的冷冻干燥可以使酶在有机溶剂中的催化活性提高1000倍。第一阶段的研究目标是改进盐激活酶的制备方法，通过测试不同反应类别的酶，包括脂肪酶、金属蛋白酶、酰胺酶、脱氢酶、氨基转移酶和糖苷酶，展示其适用范围的广度，并测量各种盐激活酶在有机溶剂中的稳定性。这项拟议的研究如果成功，将产生一种在非水溶剂中使用酶的广泛适用的方法。作为一个商业重要性的具体例子，盐激活青霉素酰胺酶将在两个关键抗生素前体的酰化反应中进行评估。该反应将为半合成β-内酰胺类抗生素的酶促合成提供一种改进的方法。拟议的商业应用：生产医药中间体和精细化学品；开发改进的生物催化剂

The discovery that enzymes can function in non-aqueous media offers the potential for expanding dramatically the usefulness of enzymes in synthetic chemistry. However, the activity of enzymes in organic media is almost always much lower than that in aqueous solutions. Since many desirable targets for enzyme-catalyzed transformations are insoluble in water, but soluble in organic solvents, low catalytic activity in organic media has thus far limited commercial applications of enzymes in synthetic chemistry. Recent research has shown that lyophilization of serine proteases in a salt matrix activates the enzymes by factors of >1000 for catalysis in organic solvents. The Phase 1 research goals are to refine the methods for preparing salt-activated enzymes, demonstrate the breadth of scope by testing enzymes from different reaction classes, including lipases, metallo-proteases, amidases, dehydrogenases, aminotransferases, and glycosidases, and measure the stability of various salt-activated enzymes in organic solvents. The proposed research would, if successful, result in a broadly applicable method for using enzymes in non-aqueous solvents. As a specific example of commercial importance, salt-activated penicillin amidase will be evaluated in the acylation of two key antibiotic precursors. This reaction will establish the feasibility of an improved method for the enzymatic synthesis of semi-synthetic beta-lactam antibiotics. PROPOSED COMMERCIAL APPLICATIONS: Production of pharmaceutical intermediates and fine chemicals; development of improved biocatalysts